Prostaglandin E.sub.2 (abbreviated as PGE.sub.2 hereinafter) has been known as a metabolite in the arachidonic acid cascade. It has been known that PGE.sub.2 has cyto-protective activity, uterine contractile activity, a pain-inducing effect, a promoting effect on digestive peristalsis, an awakening effect, a suppressive effect on gastric acid secretion, hypotensive activity and diuretic activity etc.
In the recent studies, it was found that the PGE.sub.2 receptor was divided into some subtypes which possess different roles from each other. At present, four main receptor subtypes are known and they are called EP.sub.1, EP.sub.2, EP.sub.3 and EP.sub.4, respectively (Negishi M. et al., J. Lipid Mediators Cell Signaling 12, 379-391 (1995)).
PGE.sub.2 has various kinds of physiological activities, and so it has the disadvantage that its undesired effect leads to a side effect. Research to overcome this disadvantage has been carried on by investigating the roles of each subtype and obtaining those compounds which are effective only on the subtype.
Accordingly, the present inventors investigated to find those compounds which bind on EP.sub.3 subtype receptor specifically, so that we found that 11,15-O-dialkyl prostaglandin E derivatives of formula (I) could bind specifically on EP.sub.3 receptor and hardly on other subtype receptors, and we achieved the present invention.
As to the compounds whose structures are similar to those of the compounds of the present invention of formula (I), the following techniques are known.
In JP55-115836, processes for the preparation of methyl ether derivatives are disclosed, wherein 11,15-O-dimethyl-prosta-5Z,13E-dienoic acid methyl ester is synthesized from prostaglandin E.sub.2, but nothing is described about the utility of the compounds obtained.
In JP47-42647, it is described that 15-O-alkyl ether prostaglandin E derivatives have PG-like activity. More particularly, 15-O-methyl-PGE.sub.2 is described.